Breast density and collagen alignment as predictors of DClS disease-free survival

当前乳腺癌筛查固有的高DCIS诊断率 检查过程--几乎30%的筛查发现的乳腺癌是DCIS。由于自然历史的不确定性 在DCIS中，人们普遍担心过度治疗。不幸的是，目前还不可能 确定哪些DCIS病变可能进展到潜在致命的侵袭性阶段。因此，当前 指南建议对所有患有DCIS的女性进行相对积极的治疗，包括手术、放射治疗、 考虑进行激素治疗。优化乳腺癌筛查流程，迫在眉睫 需要确定DCIS预后标记物，使个性化治疗策略成为可能。 乳房X光摄影密度是预测乳腺癌可能性的一个有前途的预后指标。 从DCIS进展到侵袭性疾病。然而，目前关于自然界的数据非常稀缺。 乳房密度和疾病进展之间的联系，以及我们理解中的许多不确定性 乳房密度的生物学机制。胶原蛋白是乳房密度的主要成分， 实验室研究表明，它在促进肿瘤侵袭方面起着关键作用。我们的目标是 一项建议是将这些实验室发现转化为乳房密度发展的进展 DCIS的预后标志物。我们的目标是1)确定乳房X光检查与乳房密度之间的关联 和女性DCIS患者的无病生存率；2)确定胶原蛋白与 DCIS患者的重组和无病生存；以及3)评估这种关联 乳房X光摄影密度与无瘤存活率之间的关系是通过胶原蛋白重组来调节的。至 为了实现这些目标，我们将使用佛蒙特州乳腺癌监测系统的数据和组织， 它包括关联的患者风险因素、乳房X光检查、病理、治疗和癌症结果数据 约1,400例DCIS病例，随访时间长达16年。我们将使用三种不同的衡量标准 乳房密度：分类BIF、DS评估、二维计算机辅助定量方法(Cumulus)、 以及三维定量体积密度评估，允许测量特定类型的乳房密度 邻近DCIS病变的感兴趣区。多光子显微镜将用于评估胶原蛋白 存档的DCIS肿瘤标本的重组。这项研究将评估乳房X光检查的潜力 乳房密度和胶原蛋白重组可作为鉴别DCIS病例的潜在标记物 有可能进展，或只需最低限度的干预即可治疗。这可能会导致大量的 提高我们将乳腺癌筛查(过度治疗)的危害降至最低的能力，同时保持 好处(降低乳腺癌发病率和死亡率)。

Elevated rates of DCIS diagnoses are inherent to current breast cancer screening processes - almost 30% of screen-detected breast cancers are DCIS. Due to uncertainty in the natural history of DCIS, there is widespread concern regarding overtreatment. Unfortunately, it is currently impossible to determine which DCIS lesions are likely to progress to a potentially lethal invasive stage. Thus, current guidelines recommend relatively aggressive treatment for all women with DCIS, including surgery, radiation, and consideration of hormone therapy. To optimize the breast cancer screening process, there is an urgent need for identification of DCIS prognostic markers that would permit personalized treatment strategies. Mammographic breast density is a promising candidate as a prognostic marker to predict the likelihood of progression from DCIS to invasive disease. Currently, however, there Is only scarce data regarding the nature of the association between breast density and disease progression, and much uncertainty in our understanding of the biological mechanisms of breast density. Collagen is a major component of breast density and laboratory studies have shown that it plays a key role in facilitating tumor Invasion. The objective of our proposal is to translate these laboratory findings into advances in the development of breast density as a prognostic marker for DCIS. We aim to 1) determine the association between mammographic breast density and disease-free survival among women with DCIS; 2) determine the association between collagen reorganization and disease-free survival among women with DCIS; and 3) assess whether the association between mammographic breast density and disease-free survival is mediated by collagen reorganization. To accomplish these aims, we will use data and tissue from the Vermont Breast Cancer Surveillance System, which includes linked patient risk factor, mammography, pathology, treatment, and cancer outcomes data for approximately 1,400 DCIS cases with up to 16 years of follow-up. We will use three different measures of breast density: the categorical BIF^DS assessment, a 2-D quantitative computer-assisted method (Cumulus), and a 3-D quantitative volumetric density assessment that permits measurement of breast density in specific regions of interest adjacent to the DCIS lesion. Multiphoton microscopy will be used to evaluate collagen reorganization in archived DCIS tumor specimens. This study will evaluate the potential for mammographic breast density and collagen reorganization to serve as potential markers for identifying DCIS cases that are not likely to progress or could be treated with only minimal intervention. This could lead to a substantial improvement in our ability to minimize the harms of breast cancer screening (overtreatment) while preserving the benefits (reductions in breast cancer morbidity and mortality).